Reverse Transcriptase

Retroviruses were originally known as RNA tumor viruses because they have RNA, not DNA, genomes, and because they were the first viruses recognized to cause certain cancers in animals. At the middle of the twentieth century, Howard Temin was interested in understanding how RNA tumor viruses cause cancer. One finding that interested him was the genetic-like stability of the uncontrolled cell growth caused by these viruses. It was known then that certain bacterial viruses, called phages, could integrate their DNA into their hosts' chromosomes and persist as stable genetic elements known as prophages. By analogy, Temin proposed the provirus hypothesis, which suggests that RNA tumor viruses can cause permanent alterations to cells by integrating into host chromosomes. In order for this to occur, Temin suggested that virion RNAs were first converted into DNAs, which could then become integrated.

The chemistry of using RNA as a template for DNA seemed possible. However, reverse transcription was at odds with the then-popular central dogma of molecular biology, advanced by Francis Crick, which maintained that genetic information flowed unidirectionally from DNA to RNA to protein. RNA tumor viruses were RNA viruses, so it was assumed that their replication involved RNA polymerases, as had been demonstrated for other RNA viruses, and not a DNA polymerase. Because his proposal of a reverse Reverse transcriptase uses a single-stranded RNA template to create a double-stranded DNA. flow of genetic information from RNA to DNA seemed heretical, and because the experimental techniques needed to test this idea were not yet developed, Temin and his hypothesis were rebuffed for many years.

The biochemical proof for reverse transcription finally arrived in 1970 when two separate research teams, one led by Temin and the other by David Baltimore, simultaneously discovered the elusive RNA-copying DNA polymerase in purified virions. In 1975 Temin and Baltimore shared the Nobel Prize in physiology or medicine for their discovery of reverse transcriptase.